Research

Suboxone vs. Vivitrol: A Head-to-Head Comparison

Buprenorphine/naloxone (brand name Suboxone) and the extended release version of naltrexone (brand name Vivitrol) both outperform placebo medication. This critically important study pitted these two commonly prescribed medications against each other.

WHAT PROBLEM DOES THIS STUDY ADDRESS?

Opioid overdoses in the U.S. have continued to increase, accounting for 33,000 overdoses in the United States in 2015 alone. Drug overdose, including but not limited to opioids, is now the leading cause of accidental death in the U.S. Certainly there is an urgent need to identify effective treatments for opioid use disorder. Buprenorphine, often prescribed in a formulation with naloxone (referred to here as the brand name Suboxone), is an opioid agonist that research shows, compared to no medication, can help reduce opioid use or protect against relapse both over the short-term as well as the long-term. Naturalistic research also suggests it may help reduce the likelihood of overdose death.

There is an ongoing need, however, to identify other helpful treatments.

First, Suboxone is better than a placebo medication, but there is room for improvement. For example, Suboxone patients in rigorous studies still produce up to 60% opioid positive urine toxicology screens (“tox” screens), with better outcomes for those who only misuse pharmaceutical opioids.

Second, like most medications, an individual needs to take buprenorphine on a daily basis – which can be problematic for individuals with substance use disorder given that motivation can be variable especially early in the recovery process.

Third, some clinicians have concerns about prescribing an opioid agonist like buprenorphine to those who are still drinking alcohol or using benzodiazepines, since they are also central nervous system depressants and, in combination, can have health consequences including overdose.

Another evidence-based medication for opioid use disorder is naltrexone, an opioid antagonist formulated as an extended-release once-a-month injection (referred to here as the brand name Vivitrol). This medication is delivered once every 4 weeks, instead of everyday and might help address concerns about needing to take the medication daily as well as the potential problems that could arise if someone is also taking other drugs (in addition to opioids) like alcohol.

One of the main concerns about naltrexone is that because it is an opioid antagonist (i.e., blocker), an individual needs to be abstinent from opioids for at least a few days so that they do not go into immediate withdrawal when administered the medication. For some individuals, this need to not use any opioids before receiving Vivitrol can be very difficult and uncomfortable, and thus can lead to resumption of illicit opioid use making this transition a clinical challenge. In this study, Lee and colleagues conducting a critically important study specifically comparing Suboxone to Vivitrol.

HOW WAS THIS STUDY CONDUCTED?

Authors used a randomized controlled trial to test Suboxone against Vivitrol in 570 individuals (287 receiving Suboxone and 283 receiving vivitrol) for 6 months who were attending one of eight inpatient detoxification programs in the U.S.

MORE ON STUDY METHODS

All participants had opioid use disorder according to the diagnostic and statistical manual of mental disorders, 5th edition (DSM-5) and had used opioids at least one of the past 30 days.

While the sites differed in terms of how they helped individuals medically withdraw from opioids (“detox”), all were short-term (3-7 days) and part of a community program that provided at least weekly therapy sessions (group or individual) on an outpatient basis during the study. The study was conducted as part of the National Institute on Drug Abuse’s Clinical Trials Network, which tests evidence-based treatments for substance use disorder in community settings. Of note, study site and severity in terms of opioid use were taken into account when randomizing patients to receive to Suboxone vs. Vivitrol.

All patients received medical management at each study visit including psychoeducation about opioid use disorder, an adherence plan, advice to abstain from all substance use, monitoring of side effects, and encouraging attendance at therapy and mutual-help groups. The medical management schedule was the same for both Suboxone vs. Vivitrol – weekly for the first month, then every two weeks for the next 3 months, then every month for the final 2 months. Suboxone doses ranged from 8 to 24 mg depending on clinical need – these are typical doses. Vivitrol was administered every 28 days, and before starting the medication, individuals needed to be abstinent from all opioids for at least 3 days, have a toxicology screen negative for opioids, and pass a “naloxone challenge” to be sure they would not withdraw from the Vivitrol.

The primary outcome was “relapse”, measured after the first 3 weeks to prevent against detoxification-related, opioid medication from being counted as opioid use, and defined as one of the following:

Secondary outcomes were failure to initiate the medication, percent days using an opioid during the 6-month study period, and adverse events including overdoses.

Characteristics of Study Sample

Important characteristics of the study sample were that they were 34 years old, on average, 70% male, 75% White and 10% Black and 13-20% Latino. Most (80%) were heroin users, more than 60% were injection drug users, and 35-40% had prior treatment. Other substance use in the past 30 days was common: 47-57% with stimulant use, 25-32% with sedative use, 42-48% with cannabis use, and 25-27% with “heavy” drinking, which was not defined by authors but, according to the Substance Abuse and Mental Health Services Administration (SAMHSA), means 5 or more drinks for men or 4 or more for women on the same occasion at least 5 days in the past month. Nearly 70% reported a lifetime history of another psychiatric disorder, and they had “mild” depressive symptoms, on average, measured by the Hamilton Depression Scale. Individuals were not able to participate in the study if they had “serious medical, psychiatric, or substance use disorder” as determined by the study physician.

WHAT DID THIS STUDY FIND?

*as verified by urine toxicology screen

In the Suboxone group, 57% relapsed during the study, significantly less than the 65% who relapsed in the Vivitrol group (i.e., unlikely due to chance – a reliably large difference). As seen in the figures below, out of 24 weekly tox screens, Suboxone individuals had 10 negative opioid tox screens, and Vivitrol individuals had four negative opioid tox screens, on average. Out of 144 days, by self-report Suboxone individuals had 81 opioid abstinent days and Vivitrol 39 abstinent days. The Suboxone group also had a significantly longer time until they relapsed, on average (14 weeks vs. 8 weeks). More specifically, in any given week, if one person was abstinent in the Suboxone group and a similar person was abstinent in the Vivitrol group, the person in the Suboxone group had a 36% higher odds of avoiding relapse that week.

One noteworthy nuance from this study is that the advantage of Suboxone occurred early – in the first 6 weeks. For those who make it past 6 weeks, Vivitrol begins to show an advantage. Another distinction is that the advantage for Suboxone appears to come from the tougher time that individuals experienced who were assigned to Vivitrol when getting started on the medication – 94% of individuals assigned to Suboxone were successfully started (also called “induction”) while only 72% of those assigned to Vivitrol were successfully started on the medication. When only the individuals successfully started on medication were analyzed, the Suboxone and Vivitrol outcomes were similar. Also, Vivitrol individuals were more likely to be successfully started on the medication if entered the study more than 3 days after the last opioid use compared to less than 3 days after their last opioid use (84% started vs 53%, respectively). So having at least a few days abstinent made a difference for Vivitrol patients.

Adverse events – including overdose – were not different between the groups. More specifically, 15 assigned to Vivitrol had an overdose (two fatal) and eight assigned to Suboxone had an overdose (three fatal). In other words, 23 of the 570 patients in the entire trial had an overdose, five of whom died, during the study period – less than 1%.

WHY IS THIS STUDY IMPORTANT

In the first 6 months after initiating a recovery attempt for opioid use disorder, Suboxone is more effective than Vivitrol at preventing relapse. This benefit is primarily accounted for by the difficulty getting individuals started on Vivitrol – which is consistent with anecdotal clinical observations and concerns. It is reasonable to think that this difficulty in getting individuals started on Vivitrol would be even more pronounced in purely outpatient settings – this study recruited individuals from inpatient opioid detox programs.

In a related study taking place in Norway that also compared Suboxone to Vivitrol, all patients had already detoxified from opioids – essentially removing any influence of needing to establish a period of abstinence to get started on Vivitrol, because it was a constant. Not surprisingly, in that study Vivitrol did as well, or in some cases, better than Suboxone. So, in settings where individuals are safely detoxified and time is not a factor (e.g., in the Veterans Administration), Vivitrol may be an equally effective option at least in the short term. On the other hand, in outpatient settings or when detoxification periods are relatively rigid – more common in addiction treatment settings – Suboxone appears to be the better option.

That said, the overall modest “success” rates – more than half relapsed in the first 6 months of this rigorously delivered, evidence-based treatment in both groups – suggest there remains much room for improvement. Researchers, clinicians, policy makers, and lay stakeholders (e.g., patients and families) will continue to need to work independently and collaboratively to find ways to improve the identification and dissemination of evidence-based treatments and other recovery support services for individuals with opioid use disorder.

LIMITATIONS

There was no group receiving a placebo medication to which to compare Suboxone and Vivitrol – however, the efficacy of each medication compared to placebo is well established.

All individuals were recruited from an inpatient detoxification program while the primary draw of each medication is that they can be initiated and prescribed on an outpatient basis.

Individuals with “serious” other psychiatric disorders – – were excluded. This decision on who to exclude was made by a study physician. Also since patients were recruited from an inpatient detoxification program, they may be more motivated for change than your average patient. This introduces two concerns. First, whether the findings from this study can be applied to the population of individuals with opioid use disorder is not clear. Second, those with more psychiatric comorbidities could have greater difficulty with day-to-day tasks, including but not limited to taking a medication. So, daily medication use may be a greater challenge, which might favor Vivitrol which is administered once every 4 weeks. Also, an agonist treatment with some – albeit minimal – potential for misuse may be more of a concern for those with other substance use disorders. Given the study design, it is not possible to answer many of these questions but they are important to applying study results and informing future work.

NEXT STEPS

There are many potential next steps in testing medication for opioid use disorder, most of which authors identified as part of a detailed summary of their study design.

Given that the medications did equally as well once started, one broad question is “For whom does each medication work best?”

For example, since Vivitrol is also used as a medication for individuals with alcohol use disorder, those with heavy drinking may do better on Vivitrol, both in terms of their drinking outcomes as well as opioid outcomes (e.g., with reduced drinking protecting against opioid relapse).

Vivitrol has been publicized widely as a potential treatment in criminal justice settings in the U.S, which have traditionally been opposed to agonist treatments like Suboxone. A paper also by Lee and colleagues showed that Vivitrol helps reduce relapse among prisoners about to be released compared to no medication.

This study tested outcomes over a 6-month period. For many with opioid use disorder, however, relapse risk remains elevated for 5 or more years. Suboxone has good long-term outcomes, with even some who were once – but are no longer – taking the medication, remaining abstinent. Whether Vivitrol has equal or better long-term outcomes to Suboxone is important to study.

The primary goal of the substantial majority of studies on medication for opioid use disorder examines only opioid outcomes. Not only are other drug – including alcohol – outcomes important to understand, but also outcomes beyond substance use, such as day-to-day functioning, employment, psychiatric symptoms, quality of life, and patient satisfaction with the treatment. Also important is the cost of each medication given its benefit – a “cost-benefit” analysis.

BOTTOM LINE

For individuals & families seeking recovery: If you or your loved one has an opioid use disorder, Suboxone and Vivitrol both may help reduce craving and protect against relapse. Vivitrol, however, may be harder to start as it requires a period of at least a few days of opioid abstinence. These medications are not cure-alls – more than half of individuals relapsed during this 6-month study, even in the highly rigorous and controlled circumstances of a clinical trial as was the case here. More research is needed to further improve outcomes for individuals with opioid use disorder.

For scientists: In this multisite randomized controlled trial comparing Suboxone to Vivitrol on relapse risk (i.e., 4 consecutive weeks of opioid use) over 6 months among individuals recently entering detoxification with a plan to transition to outpatient treatment, Suboxone outperformed Vivitrol, primarily because more individuals assigned to Suboxone were able to get started on the medication right away. While there are many potential next steps, primary among these are investigations of medication moderators, as well as how to boost medication outcomes given that even in this highly rigorous trial, more than half of the Suboxone group relapsed.

For policy makers: Suboxone and Vivitrol both help reduce craving and protect against relapse. Vivitrol, however, may be harder to start as it requires a period of at least a few days of opioid abstinence. Policies to increase the dissemination of these evidence-based medications for opioid use disorder would likely decrease the health, criminal justice, and financial burdens attributable to the opioid overdose epidemic and opioid use more broadly. Also, these medications are not cure-alls – more than half of individuals relapsed during the 6 month trial, even in the highly rigorous and controlled circumstances of a clinical trial as was the case here. Funding for research on other types of clinical and recovery support services is needed to further improve outcomes for individuals with opioid use disorder.

For treatment professionals and treatment systems: Suboxone and Vivitrol both may help reduce craving and protect against relapse. Vivitrol, however, may be harder to start as it requires a period of at least a few days of opioid abstinence. If choosing between one or the other to reduce opioid use: Suboxone is the better choice in outpatient settings, while Suboxone and Vivitrol will fare similarly, on average, in an inpatient setting, where programs have the benefit of an extended detoxification if needed. Also, these medications are not cure-alls – more than half of individuals relapsed during the 6-month trial, even in highly rigorous and controlled circumstances of a clinical trial as was the case here. More research is needed to further improve outcomes for individuals with opioid use disorder. For example, research on what types of other clinical and recovery support services can be integrated with medication to potentially improve outcomes is needed. Also, studies that investigate which individuals, in particular, may be more or less likely to benefit the most from each specific medication are needed.